{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336321/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336321"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Decoding Plasticity Regulators and Transition Trajectories in Glioblastoma with Single-cell Multiomics [ATAC-seq]","description":"Glioblastoma (GB) is incurable and resistant to therapy despite genomic stability under treatment, implicating non-genetic cellular plasticity as a central driver of progression. Whether such plasticity reflects stochastic state switching or is governed by predictable gene regulation has remained unresolved. We applied scDORI, a deep-learning framework that infers enhancer-driven gene regulatory networks at single cell resolution, to single-nucleus multi-ome profiles of over one million cells from primary GBs. Integrating computational inference with systematic gain-of-function screens across patient-derived models, we show that GB cellular plasticity is governed by a structured regulatory program with an asymmetric interplay of activators and repressors. The resulting transition landscape is hierarchical and predictable, yet permits cross-lineage trajectories absent from normal neurodevelopment. Within this landscape, low-plasticity states such as the Neuronal-like state are not stable differentiation endpoints but actively maintained configurations, stabilized by a network of safeguard repressors that silence alternate fates. MYT1L emerged as the dominant member of this network, binding and repressing master regulators of every alternative state to consolidate Neuronal-like identity. MYT1L restricted plasticity even under standard-of-care therapy and suppressed tumor growth and invasion in vivo. Conversely, MYT1L loss reactivated plasticity and accelerated malignant features, demonstrating that low-plasticity identity requires continuous repression. These findings reframe malignant cell state stability as a balance between activation and continuous repression, and nominate safeguard repressors as candidate therapeutic targets distinct from differentiation-inducing activators, with potential relevance across cancers in which phenotypic switching drives therapy resistance.","dates":{"publication":"2026/08/24"},"accession":"GSE336321","cross_references":{"GSM":["GSM9832390","GSM9832392","GSM9832391","GSM9832394","GSM9832393","GSM9832396","GSM9832395","GSM9832431","GSM9832398","GSM9832430","GSM9832397","GSM9832433","GSM9832399","GSM9832432","GSM9832435","GSM9832434","GSM9832437","GSM9832436","GSM9832439","GSM9832438","GSM9832440","GSM9832442","GSM9832441","GSM9832444","GSM9832400","GSM9832443","GSM9832325","GSM9832402","GSM9832446","GSM9832445","GSM9832401","GSM9832404","GSM9832448","GSM9832447","GSM9832403","GSM9832406","GSM9832405","GSM9832408","GSM9832407","GSM9832409","GSM9832370","GSM9832372","GSM9832371","GSM9832374","GSM9832373","GSM9832376","GSM9832375","GSM9832411","GSM9832378","GSM9832410","GSM9832377","GSM9832413","GSM9832379","GSM9832412","GSM9832415","GSM9832414","GSM9832417","GSM9832416","GSM9832419","GSM9832418","GSM9832381","GSM9832380","GSM9832383","GSM9832382","GSM9832385","GSM9832384","GSM9832387","GSM9832420","GSM9832386","GSM9832422","GSM9832389","GSM9832421","GSM9832388","GSM9832424","GSM9832423","GSM9832426","GSM9832425","GSM9832428","GSM9832427","GSM9832429"],"GPL":["30173"],"GSE":["336321"],"taxon":["Homo sapiens"]}}